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Article(id=1322934858619691470, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1322934685818564977, articleNumber=null, orderNo=null, doi=10.16016/j.2097-0927.202501065, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1737561600000, receivedDateStr=2025-01-23, revisedDate=1740931200000, revisedDateStr=2025-03-03, acceptedDate=null, acceptedDateStr=null, onlineDate=1793341849235, onlineDateStr=2026-10-30, pubDate=1743264000000, pubDateStr=2025-03-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793341849235, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793341849235, creator=13701087609, updateTime=1793341849235, updator=13701087609, issue=Issue{id=1322934685818564977, tenantId=1146029695717560320, journalId=1319373162502258839, year='2025', volume='47', issue='6', pageStart='489', pageEnd='628', issueExtLink='null', onlineDate='null', pubDate='1743264000000', pubDateStr='2025-03-30', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793341808037, creator='13701087609', updateTime=1793341808037, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=561, endPage=570, ext={EN=ArticleExt(id=1322934860645540303, articleId=1322934858619691470, tenantId=1146029695717560320, journalId=1319373162502258839, language=EN, title=Construction and evaluation of a nomogram risk prediction model for post-hepatectomy liver failure in hepatocellular carcinoma patients with hepatitis B infection at low viral load, columnId=1320435174995772212, journalTitle=Journal of Army Medical University, columnName=Clinical Medicine, runingTitle=null, highlight=null, articleAbstract=
Objective‍

To investigate the influencing factors for post-hepatectomy liver failure (PHLF) in hepatocellular carcinoma (HCC) patients with HBV infection at low viral load, and then construct a risk prediction model.

Methods‍

A total of 403 HCC patients who underwent initial hepatectomy in the First Affiliated Hospital of Army Medical University between January 1, 2015 and March 1, 2023 were recruited, and randomly assigned into a training set and a verification set in a ratio of 7:3. Lasso regression and multivariate logistic regression analyses were applied to screen the risk factors for occurrence of PHLF, and based on these identified factors, a nomogram prediction model was constructed. Receiver operating characteristic (ROC) curve analysis (area under the curve, AUC), calibration curve analysis, decision curve analysis, and clinical impact curve analysis were preformed to assess the predictive efficacy of the model.

Results‍

History of anti-viral therapy, history of drinking, logHBsAg, and international normalized ratio (INR) were independent influencing factors for the occurrence of PHLF in HCC patients with HBV infection at low viral load. The model established based on these indicators demonstrated excellent discriminative capabilities in both the training and validation sets, with an AUC value of 0.744 and 0.737, respectively. Calibration curve analysis indicated our model of high accuracy (training: P=0.995; validation: P=0.701), and decision curve analysis and clinical impact curve analysis displayed that our model provided greater clinical benefit.

Conclusion‍

Our model can effectively evaluate the risk of PHLF in HCC patients with HBV infection at low viral load, and shows good predictive performance, which has certain guiding significance for timely identification of high-risk populations.

, authors=Yan HAN, Yujie LI, Bin YI, authorsList=Yan HAN, Yujie LI, Bin YI, authorCompany=null, correspAuthors=Bin YI, authorNote=null, correspAuthorsNote=null, copyrightStatement=© 2025 Journal of Army Medical University, copyrightOwner=Editorial Office of Journal of Army Medical University, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322934866584674784, articleId=1322934858619691470, tenantId=1146029695717560320, journalId=1319373162502258839, language=CN, title=低病毒载量乙肝肝癌人群肝切除术后肝衰发生风险预测模型的建立与分析, columnId=1322185541475488183, journalTitle=陆军军医大学学报, columnName=临床医学, runingTitle=null, highlight=null, articleAbstract=
目的

探讨低病毒载量乙肝肝癌人群发生肝切除术后肝衰（post-hepatectomy liver failure，PHLF）的影响因素，并构建风险预测模型。

方法

选择2015年1月1日至2023年3月1日在陆军军医大学第一附属医院麻醉科首次接受肝切除术的403例低病毒载量乙肝肝癌患者作为研究对象，按照7∶3比例采用简单随机抽样法分为训练集和验证集，通过Lasso回归和多因素Logistic回归分析筛选PHLF发生的影响因素并建立列线图预测模型。通过多种指标对模型的性能进行评估，包括受试者工作特征曲线下面积（area under the receiver operating characteristic curve，AUC）、校准曲线、决策曲线分析和临床影响曲线分析。

结果

本研究确定抗病毒治疗史、饮酒史、乙肝表面抗原值及国际标准化比值为低病毒载量乙肝肝癌人群发生PHLF的独立影响因素。基于上述指标建立的预测模型在训练集和验证集中表现出卓越的区分能力，AUC值分别为0.744（95%CI：0.671~0.818）和0.737（95%CI：0.599~0.876）。校准曲线显示出模型的高准确性（训练集：P=0.995；验证集：P=0.701），决策曲线分析和临床影响曲线分析均表明模型提供了更大的临床益处。

结论

本研究建立的预测模型能够有效评估低病毒载量乙肝肝癌人群发生PHLF的风险，具有良好的预测性能，对及时识别高危人群具有一定的指导意义。

, authors=韩嫣, 李雨捷, 易斌, authorsList=韩嫣, 李雨捷, 易斌, authorCompany=null, correspAuthors=易斌, authorNote=

作者贡献声明

韩嫣：数据统计分析，文章撰写；李雨捷：研究指导、数据核对；易斌：研究指导、论文审阅

, correspAuthorsNote=
易斌，E-mail：
YI Bin，E-mail：
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变量PHLF组（n = 74）非PHLF组（n = 329）P
年龄/岁52.2±9.652.2±10.60.949
性别（男性）67（90.5）273（83.0）0.106
BMI/（kg/m2）22.9（4.1）23.4（3.6）0.437
吸烟史33（44.6）125（38.0）0.293
饮酒史28（37.8）79（24.0）0.015
ASA分级（Ⅲ及以上）24（32.4）76（23.1）0.093
logHBV DNA/（log10 IU/mL）0（0.3）0（0）0.418
logHBsAg/（log10 IU/mL）3.8（0.2）3.7（0.7）0.007
抗病毒治疗史15（20.3）145（44.1）<0.001
ALBI评分（2级及以上）39（52.7）108（32.8）0.001
BCLC分级（B级及以上）32（43.2）137（41.6）0.801
肝硬化史61（82.4）233（70.8）0.042
门脉高压史19（25.7）59（17.9）0.128
TBIL/（μmol/L）18.6（9.1）15.6（8.3）<0.001
ALB/（g/L）40.3（7.9）41.8（6.0）0.109
ALT/（IU/L）37.6（23.2）30.5（27.8）0.038
AST/（IU/L）35.5（20.0）32.5（20.6）0.111
ALP/（IU/L）97.0（53.0）94.0（45.5）0.236
PLT/（×10⁹/L）125.5（103.0）137.0（87.0）0.042
INR1.0（0.2）1.0（0.1）0.002
PT/（s）12.0（1.8）11.6（1.2）0.003
Cr/（μmol/L）76.1（17.8）75.3（18.1）0.558
e-GFR/（mL/min/1.73m²）96.0（17.6）97.3（18.2）0.614
甲胎蛋白/（ng/mL）74.4（1 634.5）69.4（565.6）0.325
手术方式（腔镜）31（41.9）184（55.9）0.029
麻醉方式（静吸复合）42（56.8）186（56.5）0.972
大肝切除术10（13.5）22（6.7）0.050
手术时长/min263.0（164.0）221.0（130.0）<0.001
止血药31（41.9）127（38.6）0.600
血管活性药60（81.1）258（78.4）0.612
利尿剂15（20.3）61（18.5）0.731
血制品19（25.7）46（14.0）0.013
总入量/mL2 450.0（1 333.0）2 000.0（1000.0）<0.001
总出量/mL2 100.0（1 563.0）1 600.0（975.0）<0.001
术中出血量/mL400.0（300.0）300.0（200.0）<0.001
晶-胶比0.5（0.5）0.5（0.4）0.659
尿量/mL500.0（500.0）400.0（325.0）0.016
拔管时长/min31.0（41.0）35.0（33.0）0.881
PACU时长/min84.0（59.0）85.0（45.0）0.586
苏醒时间延长24（32.4）72（21.9）0.054
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403例低病毒载量乙肝肝癌人群的基线特征大振 ［x¯±s，M（IQR），例（%）］

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变量PHLF组（n = 74）非PHLF组（n = 329）P
年龄/岁52.2±9.652.2±10.60.949
性别（男性）67（90.5）273（83.0）0.106
BMI/（kg/m2）22.9（4.1）23.4（3.6）0.437
吸烟史33（44.6）125（38.0）0.293
饮酒史28（37.8）79（24.0）0.015
ASA分级（Ⅲ及以上）24（32.4）76（23.1）0.093
logHBV DNA/（log10 IU/mL）0（0.3）0（0）0.418
logHBsAg/（log10 IU/mL）3.8（0.2）3.7（0.7）0.007
抗病毒治疗史15（20.3）145（44.1）<0.001
ALBI评分（2级及以上）39（52.7）108（32.8）0.001
BCLC分级（B级及以上）32（43.2）137（41.6）0.801
肝硬化史61（82.4）233（70.8）0.042
门脉高压史19（25.7）59（17.9）0.128
TBIL/（μmol/L）18.6（9.1）15.6（8.3）<0.001
ALB/（g/L）40.3（7.9）41.8（6.0）0.109
ALT/（IU/L）37.6（23.2）30.5（27.8）0.038
AST/（IU/L）35.5（20.0）32.5（20.6）0.111
ALP/（IU/L）97.0（53.0）94.0（45.5）0.236
PLT/（×10⁹/L）125.5（103.0）137.0（87.0）0.042
INR1.0（0.2）1.0（0.1）0.002
PT/（s）12.0（1.8）11.6（1.2）0.003
Cr/（μmol/L）76.1（17.8）75.3（18.1）0.558
e-GFR/（mL/min/1.73m²）96.0（17.6）97.3（18.2）0.614
甲胎蛋白/（ng/mL）74.4（1 634.5）69.4（565.6）0.325
手术方式（腔镜）31（41.9）184（55.9）0.029
麻醉方式（静吸复合）42（56.8）186（56.5）0.972
大肝切除术10（13.5）22（6.7）0.050
手术时长/min263.0（164.0）221.0（130.0）<0.001
止血药31（41.9）127（38.6）0.600
血管活性药60（81.1）258（78.4）0.612
利尿剂15（20.3）61（18.5）0.731
血制品19（25.7）46（14.0）0.013
总入量/mL2 450.0（1 333.0）2 000.0（1000.0）<0.001
总出量/mL2 100.0（1 563.0）1 600.0（975.0）<0.001
术中出血量/mL400.0（300.0）300.0（200.0）<0.001
晶-胶比0.5（0.5）0.5（0.4）0.659
尿量/mL500.0（500.0）400.0（325.0）0.016
拔管时长/min31.0（41.0）35.0（33.0）0.881
PACU时长/min84.0（59.0）85.0（45.0）0.586
苏醒时间延长24（32.4）72（21.9）0.054
), ArticleFig(id=1322934874570629646, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322934858619691470, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
截距和变量估计值标准误ZP值比值比95%CI
抗病毒治疗史-1.4210.411-3.4610.0010.2420.108~0.540
饮酒史0.9570.3572.6830.0072.6041.294~5.238
LogHBsAg （Log10 IU/mL）0.5020.2182.3030.0211.6521.078~2.533
INR0.5190.1673.1150.0021.6811.212~2.331
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多因素Logistic回归分析筛选独立危险因素

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截距和变量估计值标准误ZP值比值比95%CI
抗病毒治疗史-1.4210.411-3.4610.0010.2420.108~0.540
饮酒史0.9570.3572.6830.0072.6041.294~5.238
LogHBsAg （Log10 IU/mL）0.5020.2182.3030.0211.6521.078~2.533
INR0.5190.1673.1150.0021.6811.212~2.331
), ArticleFig(id=1322934874750984720, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322934858619691470, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
变量训练集（n=282）验证集（n=121）P
年龄/岁52.4±10.751.6±9.80.447
性别（男性）239（84.8）101（83.5）0.746
BMI/（kg/m2）23.3（3.8）23.2（3.6）0.573
吸烟史112（39.7）46（38.0）0.749
饮酒史70（24.8）37（30.6）0.230
ASA（Ⅲ及以上）63（22.3）37（30.6）0.079
logHBV DNA/（log10 IU/mL）0（0）0（0）0.515
logHBsAg/（log10 IU/mL）3.7（0.6）3.7（0.7）0.452
抗病毒治疗史106（37.6）54（44.6）0.186
ALBI评分（2级及以上）104（36.9）43（35.5）0.798
BCLC分级（B级及以上）123（43.6）46（38.0）0.296
肝硬化史207（73.4）87（71.9）0.755
门脉高压史57（20.2）21（17.4）0.506
TBIL/（μmol/L）16.0（8.7）16.0（7.9）0.528
ALB/（g/L）41.5（6.3）42.1（6.4）0.330
ALT/（IU/L）32.3（27.5）30.5（27.0）0.340
AST/（IU/L）33.1（22.4）32.7（15.2）0.294
ALP/（IU/L）95.0（50.0）94.0（47.0）0.401
PLT/（×10⁹/L）139.0（87.0）132.0（90.0）0.743
INR1.0（0.1）1.0（0.1）0.880
PT/s11.6（1.3）11.6（1.2）0.889
Cr/（μmol/L）75.6（17.8）75.0（18.6）0.502
e-GFR/（ mL/min/1.73m²）96.8（19.1）96.9（16.2）0.902
甲胎蛋白/（ng/mL）55.6（576.8）118.2（722.1）0.060
手术方式（腔镜）158（56.0）57（47.1）0.100
麻醉方式（静吸复合）161（57.1）67（55.4）0.749
大肝切除术24（8.5）8（6.6）0.518
手术时长/min233.0（140.0）226.0（128.0）0.493
止血药112（39.7）46（38.0）0.749
血管活性药227（80.5）91（75.2）0.233
利尿剂54（19.1）22（18.2）0.820
血制品44（15.6）21（17.4）0.661
总入量/mL2 100.0（1020.0）2 100.0（1200.0）0.731
总出量/mL1 700.0（995.0）1 600.0（1125.0）0.484
术中出血量/mL300.0（263.0）300.0（300.0）0.870
晶-胶比0.5（0.4）0.5（0.3）0.372
尿量/mL400.0（300.0）500.0（300.0）0.845
拔管时长/min38.0（34.0）32.0（31.0）0.080
PACU时长/min86.0（54.0）79.0（47.0）0.054
苏醒时间延长71（25.2）25（20.7）0.329
), ArticleFig(id=1322934874918756881, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322934858619691470, language=CN, label=表3, caption=

训练集和验证集的基本特征 ［x¯±s，M（IQR），例（%）］

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变量训练集（n=282）验证集（n=121）P
年龄/岁52.4±10.751.6±9.80.447
性别（男性）239（84.8）101（83.5）0.746
BMI/（kg/m2）23.3（3.8）23.2（3.6）0.573
吸烟史112（39.7）46（38.0）0.749
饮酒史70（24.8）37（30.6）0.230
ASA（Ⅲ及以上）63（22.3）37（30.6）0.079
logHBV DNA/（log10 IU/mL）0（0）0（0）0.515
logHBsAg/（log10 IU/mL）3.7（0.6）3.7（0.7）0.452
抗病毒治疗史106（37.6）54（44.6）0.186
ALBI评分（2级及以上）104（36.9）43（35.5）0.798
BCLC分级（B级及以上）123（43.6）46（38.0）0.296
肝硬化史207（73.4）87（71.9）0.755
门脉高压史57（20.2）21（17.4）0.506
TBIL/（μmol/L）16.0（8.7）16.0（7.9）0.528
ALB/（g/L）41.5（6.3）42.1（6.4）0.330
ALT/（IU/L）32.3（27.5）30.5（27.0）0.340
AST/（IU/L）33.1（22.4）32.7（15.2）0.294
ALP/（IU/L）95.0（50.0）94.0（47.0）0.401
PLT/（×10⁹/L）139.0（87.0）132.0（90.0）0.743
INR1.0（0.1）1.0（0.1）0.880
PT/s11.6（1.3）11.6（1.2）0.889
Cr/（μmol/L）75.6（17.8）75.0（18.6）0.502
e-GFR/（ mL/min/1.73m²）96.8（19.1）96.9（16.2）0.902
甲胎蛋白/（ng/mL）55.6（576.8）118.2（722.1）0.060
手术方式（腔镜）158（56.0）57（47.1）0.100
麻醉方式（静吸复合）161（57.1）67（55.4）0.749
大肝切除术24（8.5）8（6.6）0.518
手术时长/min233.0（140.0）226.0（128.0）0.493
止血药112（39.7）46（38.0）0.749
血管活性药227（80.5）91（75.2）0.233
利尿剂54（19.1）22（18.2）0.820
血制品44（15.6）21（17.4）0.661
总入量/mL2 100.0（1020.0）2 100.0（1200.0）0.731
总出量/mL1 700.0（995.0）1 600.0（1125.0）0.484
术中出血量/mL300.0（263.0）300.0（300.0）0.870
晶-胶比0.5（0.4）0.5（0.3）0.372
尿量/mL400.0（300.0）500.0（300.0）0.845
拔管时长/min38.0（34.0）32.0（31.0）0.080
PACU时长/min86.0（54.0）79.0（47.0）0.054
苏醒时间延长71（25.2）25（20.7）0.329
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低病毒载量乙肝肝癌人群肝切除术后肝衰发生风险预测模型的建立与分析
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韩嫣 , 李雨捷 , 易斌
陆军军医大学学报 | 临床医学 2025,47(6): 561-570
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陆军军医大学学报 |临床医学 2025 , 47 (6) : 561 -570
低病毒载量乙肝肝癌人群肝切除术后肝衰发生风险预测模型的建立与分析
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韩嫣, 李雨捷, 易斌
作者信息
  • 1陆军军医大学（第三军医大学）第一附属医院麻醉科，重庆
通讯作者:
易斌，E-mail：
YI Bin，E-mail：
作者简介:

作者贡献声明

韩嫣：数据统计分析，文章撰写；李雨捷：研究指导、数据核对；易斌：研究指导、论文审阅

Construction and evaluation of a nomogram risk prediction model for post-hepatectomy liver failure in hepatocellular carcinoma patients with hepatitis B infection at low viral load
Yan HAN, Yujie LI, Bin YI
Affiliations
  • 1Department of Anesthesiology，First Affiliated Hospital，Army Medical University （Third Military Medical University），Chongqing，China
出版时间: 2025-03-30 doi: 10.16016/j.2097-0927.202501065
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摘要
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目的

探讨低病毒载量乙肝肝癌人群发生肝切除术后肝衰（post-hepatectomy liver failure，PHLF）的影响因素，并构建风险预测模型。

方法

选择2015年1月1日至2023年3月1日在陆军军医大学第一附属医院麻醉科首次接受肝切除术的403例低病毒载量乙肝肝癌患者作为研究对象，按照7∶3比例采用简单随机抽样法分为训练集和验证集，通过Lasso回归和多因素Logistic回归分析筛选PHLF发生的影响因素并建立列线图预测模型。通过多种指标对模型的性能进行评估，包括受试者工作特征曲线下面积（area under the receiver operating characteristic curve，AUC）、校准曲线、决策曲线分析和临床影响曲线分析。

结果

本研究确定抗病毒治疗史、饮酒史、乙肝表面抗原值及国际标准化比值为低病毒载量乙肝肝癌人群发生PHLF的独立影响因素。基于上述指标建立的预测模型在训练集和验证集中表现出卓越的区分能力，AUC值分别为0.744（95%CI：0.671~0.818）和0.737（95%CI：0.599~0.876）。校准曲线显示出模型的高准确性（训练集：P=0.995；验证集：P=0.701），决策曲线分析和临床影响曲线分析均表明模型提供了更大的临床益处。

结论

本研究建立的预测模型能够有效评估低病毒载量乙肝肝癌人群发生PHLF的风险，具有良好的预测性能，对及时识别高危人群具有一定的指导意义。

低病毒载量乙肝肝癌人群  /  肝切除术后肝衰  /  Lasso  /  列线图  /  预测模型
Objective‍

To investigate the influencing factors for post-hepatectomy liver failure (PHLF) in hepatocellular carcinoma (HCC) patients with HBV infection at low viral load, and then construct a risk prediction model.

Methods‍

A total of 403 HCC patients who underwent initial hepatectomy in the First Affiliated Hospital of Army Medical University between January 1, 2015 and March 1, 2023 were recruited, and randomly assigned into a training set and a verification set in a ratio of 7:3. Lasso regression and multivariate logistic regression analyses were applied to screen the risk factors for occurrence of PHLF, and based on these identified factors, a nomogram prediction model was constructed. Receiver operating characteristic (ROC) curve analysis (area under the curve, AUC), calibration curve analysis, decision curve analysis, and clinical impact curve analysis were preformed to assess the predictive efficacy of the model.

Results‍

History of anti-viral therapy, history of drinking, logHBsAg, and international normalized ratio (INR) were independent influencing factors for the occurrence of PHLF in HCC patients with HBV infection at low viral load. The model established based on these indicators demonstrated excellent discriminative capabilities in both the training and validation sets, with an AUC value of 0.744 and 0.737, respectively. Calibration curve analysis indicated our model of high accuracy (training: P=0.995; validation: P=0.701), and decision curve analysis and clinical impact curve analysis displayed that our model provided greater clinical benefit.

Conclusion‍

Our model can effectively evaluate the risk of PHLF in HCC patients with HBV infection at low viral load, and shows good predictive performance, which has certain guiding significance for timely identification of high-risk populations.

HCC patients with HBV infection at low viral load  /  post-hepatectomy liver failure  /  Lasso  /  nomogram  /  prediction model
韩嫣, 李雨捷, 易斌. 低病毒载量乙肝肝癌人群肝切除术后肝衰发生风险预测模型的建立与分析. 陆军军医大学学报, 2025 , 47 (6) : 561 -570 . DOI: 10.16016/j.2097-0927.202501065
Yan HAN, Yujie LI, Bin YI. Construction and evaluation of a nomogram risk prediction model for post-hepatectomy liver failure in hepatocellular carcinoma patients with hepatitis B infection at low viral load[J]. Journal of Army Medical University, 2025 , 47 (6) : 561 -570 . DOI: 10.16016/j.2097-0927.202501065
正文
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肝细胞癌（肝癌）是世界第六大常见癌症，也是导致癌症相关死亡的第四大原因［1］。目前为止，肝切除术仍是肝癌患者最主要的一线治疗方法［2-3］，尽管随着外科技术和手术设备的进步，肝切除术后死亡率已降低到不到5%［4］，然而术后并发症的发生率仍然很高，为20%~70%［5］，其中肝切除术后肝衰竭（ost-hepatectomy liver failure，PHLF）是最严重的并发症之一，因此确定与PHLF相关的相关影响因素对于改善肝癌患者肝切除术的预后至关重要。
中国大陆63.9%的肝癌由乙型肝炎病毒（hepatitis B virus，HBV）感染导致［6］，大量研究结果显示合并HBV感染，尤其是处于高病毒载量状态的肝癌患者，接受肝切除术后的预后往往较非乙肝肝癌患者差［7］。而抗病毒治疗作为乙肝感染的主要治疗方法，已被证明可以阻断HBV DNA（hepatitis B virus deoxyribonu-cleic acid）复制，减轻肝脏炎症，并防止HBV再激活，从而改善预后［8］。然而HBV感染患者接受或不接受抗病毒治疗的管理策略存在差异，亚太肝脏研究协会指南建议仅在血清HBV DNA水平≥2 000 IU/mL时才进行抗病毒治疗［9］。因此低病毒载量人群（血清HBV DNA水平<2 000 IU/mL）常被视作相对低风险人群［10-11］，其发生PHLF的危险因素以及是否能通过术前抗病毒治疗改善术后结局尚不明确。列线图模型为近年常用的预测模型，该模型是在Logistic回归模型基础上发展而来，操作更加简便、易行，更适用于个性化预测，因此本研究旨在通过建立低病毒载量乙肝肝癌人群PHLF发生风险预测模型，为指导临床对此类人群进行个性化干预提供参考。
1　资料与方法
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1.1　研究对象
选择2015年1月1日至2023年3月1日在陆军军医大学第一附属医院麻醉科首次接受肝切除术的肝细胞癌患者进行回顾性病例对照研究。纳入标准：①年龄超过18岁；②病理活检确诊为肝细胞癌；③首次接受肝切除术；④术前乙肝病毒载量（HBV DNA）<2 000 IU/mL；⑤接受全身麻醉。排除标准：①有HCV-Ab/TP感染史；②有肝外转移；③接受急诊手术；④术前接受过抗肿瘤治疗；⑤拟分析相关数据缺失超过30%。研究方案已于2024年7月5日获得陆军军医大学第一附属医院伦理委员会的批准［批件号：（B）KY2024206］，并获得书面知情同意豁免。
1.2　数据收集
从麻醉信息管理系统和电子病历中提取变量：①术前特征包括年龄、性别、身高、体质量、吸烟史和饮酒史、现病史和既往病史；实验室数据（术前最接近手术日期的数据）包括白蛋白（albumin，ALB）、总胆红素（total bilirubin，TBIL）、天门冬氨酸氨基转移酶（aspartate aminotransferase，AST）、丙氨酸氨基转移酶（alanine aminotransferase，ALT）、碱性磷酸酶（alkaline phosphatase，ALP）、血小板（platelet，PLT）、国际标准化比值（international normalized ratio，INR）、凝血酶原时间（prothrombin time，PT）、估算肾小球滤过率（estimated glomerular filtration rate，e-GFR）、肌酐（creatinine，Cr）等；②术中变量包括手术方式、麻醉方式、手术和麻醉持续时间、术中肝门阻断次数和持续时间、病理结果、出入量等；③术后变量包括拔管时间、麻醉后恢复室（post-anesthesia care unit，PACU）停留时间、术后住院时间、术后重症监护室（intensive care unit，ICU）停留时间等；④与HBV相关的变量包括HBV DNA、乙肝表面抗原（hepatitis B surface antigen，HBsAg）以及规律抗病毒治疗史（anti-viral therapy，AVT）。AVT定义为患者在术前接受超过半年的规律AVT治疗，对药物类型和剂量没有限制。
1.3　诊断标准
PHLF诊断依据2011年国际肝脏外科研究小组（international study group of liver surgery，ISGLS）归纳总结了50项关于PHLF研究从而提出的PHLF的统一定义。其定义为：术后肝脏合成、分泌、解毒等功能受损，主要以TBIL和INR为评估标准。即术后第5天或之后TBIL和INR值升高且大于术前值时，诊断为术后肝衰竭，以上情况均排除胆道梗阻［12］。根据指南对研究对象的美国麻醉师协会分级（American Society of Anesthesiologists，ASA）［13］、巴塞罗那分期（Barcelona clinic liver cancer，BCLC）［14］、白蛋白-胆红素评分（albumin-bilirubin，ALBI）［15］以及大肝切除术［16］重新进行了分级。苏醒时间延长定义为术后PACU停留时间超过2 h。
1.4　统计方法
所有的数据分析通过R （version 4.4.2）和SPSS （version 27.0）完成。所有统计检验为双侧检验，P<0.05被视为差异具有统计学意义。根据变量类型及其分布对数据进行了分析和呈现。对于分类变量，使用Pearson’s χ2检验或Fisher精确检验进行评估并通过例（%）的形式呈现。对于连续变量，使用Mann-Whitney U检或t检验进行评估并通过x¯±s或M（IQR）形式呈现。采用Lasso回归和Logistic回归2种分析方法来探讨观察指标与PHLF之间的关系。本文采取经验法10*EPV （event per variable）确定训练集样本量［17］，将研究对象以7:3比例简单随机抽样分为训练集和验证集，训练集用以构建模型，验证集用以进行内部验证。再利用“glmnet”包来进行Lasso回归以从大量潜在的多重共线性变量中选取具有非零系数的变量，用以构建Logistic回归模型。使用“rms”包，将Logistic回归中具有统计学意义的变量用以开发列线图预测模型，并使用“shinyPredict”包生成网页版动态列线图以提高模型实用性。随后计算模型的受试者工作特征曲线下面积（area under the receiver operating characteristic curve，AUC）、灵敏度、特异度、最佳截断值、阳性预测值和阴性预测值。同时通过生成校准曲线来评估模型预测概率与观察概率之间的一致性。为了确定模型在临床环境中的实际应用效果，进行决策曲线分析。绘制临床影响曲线，以直观展示模型在不同阈值条件下的表现。
2　结果
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2.1　参与者的基线特征
本研究共纳入403例符合纳排标准的患者，其中74例患者确诊为PHLF，患病率为18.4%。单因素分析结果显示：2组患者饮酒史、logHBsAg、抗病毒治疗史、ALBI分级（2级及以上）人群占比、肝硬化史、TBIL、ALT、PLT、INR、PT、手术方式（腔镜）人群占比、手术时长、血制品使用史、总入量、总出量、术中出血量及尿量均具有统计学意义（P<0.05），见表1。
2.2　PHLF发生的独立影响因素筛选
将是否发生PHLF作为因变量，将表1中各指标作为自变量，通过lasso回归进行有效的变量筛选，最终筛选出8个Lasso回归中的非零系数变量，分别是：抗病毒治疗史、饮酒史、LogHBsAg、ALBI分级（2级及以上）、手术时长、总出量、INR水平及甲胎蛋白水平（图1、图2）。随后，将Lasso回归筛选出的非零系数变量作为自变量，进行多因素Logistic回归分析。结果如表2所示，抗病毒治疗史、饮酒史、logHBsAg、INR水平是低病毒载量乙肝肝癌患者肝切除术后发生肝衰的独立影响因素（P<0.05）。
2.3　列线图模型构建
基于上述影响因素构建低病毒载量乙肝肝癌患者肝切除术后肝衰发生风险预测的静态列线图模型（图3）。通过计算出各个变量得分的总和，然后将其映射到列线图的总分轴上，即可确定个体发生PHLF的概率。例如，一位术前接受抗病毒治疗的患者，有饮酒史，logHBsAg为3.9 log10 IU/mL，INR为0.98，最后4个预测变量得分的总和为139，表明其发生PHLF的概率为14.4%。
同时生成网页版动态列线图，点击此网址https://anti-viralresearch.shinyapps.io/xiaobao/，进入后选择相应的变量选项，即可得到相应特征患者的PHLF发生概率及其95%CI。
2.4　验证组患者与训练组的基线特征
将所有研究对象以7∶3比例随机分为训练集（n=282）和验证集（n=121），其中验证集中共有22例患者（18.2%）发生PHLF。据统计，验证集的基本特征与训练集差异无统计学意义（P>0.05，表3）。
2.5　模型的性能评估
为了评估模型的预测能力，绘制模型的ROC曲线（图4A）。以训练集构建低病毒载量乙肝肝癌患者肝切除术后肝衰发生预测模型预测值的AUC为0.744，95%CI为0.671~0.818；敏感度为61.5%，特异度为77.8%，阳性预测值为38.6%，阴性预测值为89.9%；提示此模型具有一定的区分能力。以验证集数据进行内部验证，由其构建的模型AUC为0.737，95%CI为0.599~0.876；敏感度为77.3%，特异度为68.7%，阳性预测值为35.4%，阴性预测值为93.2%，与训练集结果相接近（图4B）。
校准性能：图5展示了模型在训练集与验证集中的校准曲线。从图中可以清晰看出，这2条校准曲线与理想的45°线贴合度高（训练集：P=0.995，Brier=0.131；验证集：P=0.701，Brier=0.121），模型预测结果与观察结果之间均不存在显著性差异。这充分证明模型经过了良好的校准，其预测概率与实际结果高度一致，展现出了卓越的性能。
临床实用性：决策曲线分析结果显示，当列线图模型预测低病毒载量乙肝肝癌患者肝切除术后肝衰发生风险的概率阈值为0.10~0.50时，患者的净收益率>0（图6）。此外，模型的临床影响曲线显示，当风险阈值设定在0.4以上时，模型判定为PHLF的高风险人群与实际发生PHLF的人群高度匹配（图7）。这充分凸显了模型在临床应用中的有效率较高。综上所述，此模型不仅预测能力出众，而且具有显著的临床应用价值，为在更广泛的风险阈值范围内做出医疗决策提供了有力的支持。
3　讨论
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随着手术技术和围术期管理的进步，肝切除术的安全性和术后结局得到了极大的提高，但术后肝衰竭仍是术后死亡的主要原因之一，其发生率在0.7%~34%［18］，这与本研究中的患病率（18.4%）相符。研究表明，合并HBV感染的肝癌患者肝切除术后预后更差，且PHLF的发生率高于非乙肝患者，其中高病毒载量状态被证实是PHLF发生的危险因素。而低病毒载量乙肝肝癌人群往往被人们所忽略［19］，目前鲜少有研究报道此人群肝切除术后结局及影响因素，因此若能早期识别低病毒载量乙肝肝癌人群PHLF发生风险具有重要的意义。
本研究将Lasso回归筛选出的影响因素作为自变量，进行多因素Logistic回归分析，结果显示：抗病毒治疗史、饮酒史、logHBsAg、INR是低病毒载量乙肝肝癌人群PHLF发生的独立影响因素。①HBV感染患者是否需要进行抗病毒治疗仍有争议，一些研究表明，血清HBV-DNA水平<2 000 IU/mL的患者预后较好，不适合抗病毒治疗［10-11］，亚太肝脏研究协会指南也建议仅在血清HBV DNA水平≥2 000 IU/mL时才进行抗病毒治疗［9，20］。与此同时，抗病毒治疗已被证明有利于高水平HBV DNA的HBV乙肝相关肝癌根治性肝切除术后的长期生存［21］。基于此，一些研究开始讨论抗病毒治疗对低HBV DNA水平肝癌患者长期预后的影响，并得出了类似的结论［22］。本研究所建立的预测模型显示抗病毒治疗是此类患者PHLF发生的保护因素，从而得出即使HBV DNA水平<2 000 IU/mL，术前抗病毒治疗也是有益的结论。这也符合美国肝脏研究协会和欧洲肝脏研究协会的指导方针［23-24］。②饮酒史对于低病毒载量乙肝肝癌患者PHLF发生也有重要的影响。报道称饮酒会造成不同程度的肝损伤，这可能使本就肝功异常的低病毒载量乙肝肝癌患者肝功能进一步受损，增加PHLF发生的风险［25］。③本研究显示乙肝表面抗原同样是低病毒载量乙肝肝癌人群PHLF发生的危险因素，研究表明HBsAg在HBV感染的发展和进程中发挥了关键作用，它不仅导致病毒持续存在，还会破坏免疫反应，从而引起肝功能受损，使患者在接受肝切除术后更易发生肝衰竭或其他术后并发症［26］。这可能为仍在研究中的三联组合疗法（抑制病毒复制、降低病毒抗原负担以及免疫刺激）提供了临床依据，以用于HBV感染患者的治疗［27］。④在本研究中，INR也是预测低病毒载量乙肝肝癌个体发生PHLF的关键指标。INR作为衡量凝血功能的指标，也能侧面反映肝脏功能。最近，APASL ACLF研究联盟得出并内部验证的AARC评分，该评分纳入了INR，临床上用于评估严重肝病患者的预后，显示出相当好的预测能力［28］。ISGLS于2011年提出了PHLF的定义，该定义具有可靠的预后价值，其诊断依赖于术后5 d及以上的TBIL及INR水平的升高，但若此时干预可能为时已晚［29］。因此本研究将术前INR值纳入了预测模型，并得出了术前INR水平的异常会增加PHLF发生的风险。
列线图模型实现了Logistic回归的可视化，该模型因有可视化、计算方便的优势而在近年得到了广泛的应用［30-31］。列线图模型不仅明确了低病毒载量乙肝肝癌患者PHLF发生的影响因素，还为每位患者提供了个性化预测，计算出其PHLF发生的风险，满足患者个性化医疗的需求。且本研究集中在低病毒载量乙肝肝癌人群上，为这类人群建立了PHLF的列线图预测模型，可以帮助减少此类患者的漏诊率。但模型仅进行了内部验证，缺少样本量更大、多中心数据的外部验证，需要更多前瞻性研究及数据来优化列线图预测模型，更有利于临床应用的推广。
综上所述，低病毒载量乙肝肝癌患者PHLF发生主要受术前是否抗病毒治疗、饮酒史、乙肝表面抗原值、INR水平的影响，基于上述因素建立的预测模型具有较高的准确度和区分度。

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2025年第47卷第6期
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doi: 10.16016/j.2097-0927.202501065
  • 接收时间：2025-01-23
  • 首发时间：2026-10-30
  • 出版时间：2025-03-30
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  • 收稿日期：2025-01-23
  • 修回日期：2025-03-03
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    1陆军军医大学（第三军医大学）第一附属医院麻醉科，重庆

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2种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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